The goals of the project are to characterize the pathogenesis, natural history and therapy of herpes simplex virus and varicella-zoster virus infections. Our clinical emphasis has been on genital herpes in normal and immune-impaired patients. Analysis of 7 years of suppressive acyclovir therapy in patients with frequently recurring herpes have shown the drug to remain effective, to be well-tolerated, and to not induce drug resistance. We continue to study the ability of ultraviolet light and other physical and chemical agents to induce recurrent herpes simplex infections in humans. In a placebo-controlled trial, acyclovir was found to significantly block u-v induced reactivation of HSV-2 infection. A placebo-controlled trial of acyclovir for suppression of frequent, spontaneously recurring oral herpes is near completion. The major thrust or our laboratory effort in this project has been the analysis of HSV latency in human ganglia. We demonstrated and further characterized latent HSV-2 RNAs in sacral ganglia during the past year. Further efforts to define the structure, kinetics, and regulation of these latency-associated RNAs and their promoters are underway.